Journal Issue: Vol.8, No.2 - April 2009

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Editorial: The Role of Scientific Journals in Disseminating Cancer Research in the 21st Century

Dr. Loredana Marcu University of Oradea, Faculty of Science, Department of Physics, Romania University of Adelaide, School of Chemistry and Physics, SA 5000, Australia "Research is to see what everybody else has seen, and to think what nobody else has thought" (Nobel Prize winner for Medicine, Albert Szent-Gyvrgyi). Clinical and scientific research are the bread and butter of today's advancements in oncology, proving the fact that several researchers have "thought" what nobody else has imagined before. Thanks to these pioneers, we now have a flourishing discipline which has focused the interest of tens of thousands of scientific investigators, all having the same goal: to cure cancer. While research per se is the first step towards the final aim, disseminating the results and making the findings public are key factors in the process. Scientific journals have always played a crucial role in broadcasting research outcomes. Before the dawn of the digital age the only possibility of publishing was printed issue and this physical medium dictated the speed with which new information reached scientists, but one of the major technological feats of the last century, the Internet, has allowed today an incomparably broader and speedier exposure of the journals. While in some areas of science the corresponding journals have managed to keep pace with the new developments thus timely publishing the results, in other areas, such as oncology, despite the fact that the number of journals has greatly increased, there are way-too-long lists of articles to-be-published after acceptance. This is the result of the exponential growth of oncology research, compared to the smoother, more linear development of other disciplines, which led to the journals being "bombarded" with articles, forcing editors to reorganize the structure of the journal to allow for rapid communications when breakthrough results need publishing. The last few decades have been marked by significant changes in all areas of oncology. The desperate need to better manage cancer patients brought together clinicians, medical scientists, radiotherapists, nurses and engineers, all aiming towards improved treatment outcome, whether radiotherapy, chemotherapy, molecular targeted therapy or surgery. Radiobiology has proven its merits as the science behind radiotherapy through the impressive evolution this discipline has undergone over the last 30 years. Evolving from the basic knowledge of radiation interaction with matter described by the target theory, to the latest discoveries regarding chromosomal aberrations and formation of micronuclei after radiation exposure, radiobiology has traveled a long way, from obscurity into clinical practice. In radiotherapy, the "transformation" of cobalt machines into well advanced linear accelerators equipped with multileaf collimators and on-board imaging systems has allowed the professionals to perform highly conformal radiotherapy, by modulating the intensity of the beam and avoiding surrounding critical structures. The advances in targeted cancer therapy from signal transduction inhibitors and biologic response modifiers through the development of monoclonal antibodies and anti-angiogenesis inhibitors brought new hopes in using the body's natural defense systems to fight against cancer. The fusion of sciences such as physics and biology, engineering and genetics, mathematics and molecular sciences and also the need for broader knowledge in all areas led to the advent of interdisciplinarity. New research groups have been created which have found new investigation avenues in oncology. New questions kept arising waiting for groundbreaking answers. Several times clinicians and scientists have been challenged by situation of finding the needle in the haystack and several times they succeeded. State-of-the-art results followed and dissemination of the findings became indispensable for future developments in that research area. Several oncology journals cover quite wide research areas, from bench to clinical trials. While for the reader who is getting the "big picture" of the latest research highlights from one periodical these journals are of high value, the editors are challenged to put in balance high quality research results from different sub-disciplines. Due to the restricted number of articles per issues, it is hard to decide which communications/articles from the large amount received should have publication priority for faster dissemination. While clinical trial outcomes are needed to be published in an efficient manner to help clinicians in deciding upon treatment regimens, important pre-clinical study results are needed to be out in the open in order to allow future clinical implementation. Also, results of theoretical modelling in radiobiology need publishing for further validation by cell lines experiments and, at the same time, cell line findings have to be publicized to assist pre-clinical research. A research area of great importance is cancer epidemiology as it is of crucial significance for the epidemiological data and risk factors in oncology to be timely broadcasted considering that over one third of cancers are preventable. Indisputably, prevention offers the most health- and cost-effective approach to control cancer as it is much better and easier to prevent than to treat. In today's fast paced world it can become a challenge to timely publish cutting edge results. The multitude of findings, whether theoretical or experimental, pre-clinical or clinical, tumour or normal tissue-related, create an avalanche of articles which are placing journal editors in front of difficult decisions. Editing and coordinating a scientific journal is a demanding job. Editors have to keep pace with the latest research interests and with the scientific community's demands in order to coordinate the editorial board's work accordingly. Perhaps the major challenge facing the editors is the management of the large volume of articles received, as the editor represents the first level of assessment in selecting the valuable and novel work. An equally great task is the establishment of a team of knowledgeable reviewers able to assess others' work in an unbiased, critical but fair, objective and open-minded manner. Besides creating the appropriate environment to publish articles with high scientific content, the editor has to ensure the timely publishing of the selected papers. Being responsible for the articles under review, the editor has to oversee the work of the reviewers so they complete their agreed duties within well defined timelines. There is no bigger frustration for a researcher wishing to publish long awaited results than to learn that others have arrived at the same outcome later, but have published them earlier due to prompter reviewing process. In other words, a successful journal needs a well structured selection and review mechanism, with well devised timelines that are adhered to by all involved. Another element of the editorial process that is critical for the success of a journal in today's fast developing world is the communication with authors. Good communication leads to higher efficiency. Therefore, a well designed and highly functional journal website is crucial to alleviate article submission and follow up. Nowadays, the majority of the periodicals allow on-line submission which is, undoubtedly, a step towards faster publication. It is important for the online submission process to be easy and efficient, focusing on content rather than form. Once the possibility to follow up the status of the article is introduced, the journal editor has to ensure that the process is functional and the status of the paper is updated whenever needed, adhering to the previously emphasized timelines. Although there is a large number of valuable articles that result from the selection and review process, there is a limited number of articles that can be published in a printed issue. This physical limitation can be circumvented by turning towards online publishing where all selected articles could be published. With this approach, good quality research could be broadcasted around the scientific community in a very short time, allowing for faster feedback and also for faster implementation of the findings whenever appropriate. As for many people the Internet is synonymous with free and unrestrained access, it is not surprising that journals having open access to their articles are warmly welcomed by the scientific communities. The challenge here is to make this transition towards the online medium in a financially sustainable way, to find a solution that combines the economically viable subscription model with the open access ideals that many researchers would welcome. A midway solution could be to make available the recent articles for subscribers only and have older articles freely accessible. Timely publication of scientific and clinical research is therefore critical. Journals and editors are faced with several challenges to achieve high quality in their endeavours. Since research and dissemination of results are critical factors in the progress of mankind, journals bear great responsibility by playing a key role in this process. A well organised editorial board collaborating with a knowledgeable team of open-minded but critical reviewers can surmount the challenges of efficiently publishing good quality research findings and gain recognition from the scientific community. Research is a process of investigation and the road towards development. Oncological research has traveled a long way, from the basic cancer biology to treatment outcome assessment making large steps due to the brilliance of the researchers involved. In the last few decades a technological instrument has greatly accelerated the pace of development in oncology. This technological feat is the computer. The personal computer is used in almost every stage of pre-clinical and clinical research starting from cell biology studies to treatment planning and data analysis. The computers are now on course to revolutionise the way research results are disseminated through the scientific community. Cancer research is fast developing due to the endless effort of a large number of devoted professionals whose continuous enthusiasm is bringing this discipline closer to the final goal: to prevent and cure cancer. Every day, we are getting closer and closer to the answers we are looking for, thanks to the ambition of researchers in obtaining breakthrough results, the commitment of clinicians in implementing them, and the hard work of editors to disseminate the relevant information to the whole scientific community. And we all have to keep doing what we are doing because: "Somewhere something incredible is waiting to be known." (Carl Sagan). Dr. Loredana Marcu


Profile: Dr Ancha Baranova

Ancha Baranova, a specialist in the area of functional genomics of complex human diseases, is presently working as an Associate Professor in the Molecular and Microbiology Department, College of Science, George Mason University in Fairfax, Virginia, USA. She was born on June 10, 1971 in Penza, Russia. Dr. Baranova graduated from Moscow State University (Moscow, Russia) in 1995 with an MS in Biochemistry/Virology with a thesis on the physical mapping of human chromosome 13. She continued her MS project with her PhD and received a PhD in Virology from Moscow State University in 1998. Since her sophomore year in MSU and till 2002 she worked in the Vavilov Institute of General Genetics (VIGG), Moscow, Russia under the supervision of recognized geneticist Prof. Nick Yankovsky. She started at VIGG in 1991 as a Research Assistant, and then moved through a number of projects, interim positions, and degrees awarded, finally advancing to the position of Senior Scientist and Functional Genomics Group Leader. In 2004, Dr. Baranova received a Doctor of Sciences degree in 2004 from VIGG (Russian Academy of Sciences). D. Sci. is a post-doctoral degree that has no Western equivalent. Dr. Baranova relocated to the United States in 2002 after she joined the Molecular and Microbiology Department (George Mason University, Fairfax, VA) as a tenure-track Assistant Professor. In 2007 Dr. Baranova received tenure and was promoted to Associate Professor. In addition, since 2005 Dr. Baranova serves as Assistant Director of the Center for Study of the Genomics of Liver Disease in the College of Sciences, George Mason University. Dr. Baranova's major academic contributions are in the field of functional genomics, with emphasis on cancer and metabolic syndrome-related disorders. Since 1992 she has participated in international collaborations aimed at the positional cloning of the tumor suppressor gene rearranged in B-cell chronic lymphocytic leukemia. Luckily, while other scientists concentrated on the genes located within minimally deleted area, Dr. Baranova and her Team worked on adjacent genes that seemed secondary candidates at best. When experimental studies revealed that the primary candidates had no open reading frames, Dr. Baranova's candidates moved into focus. The fine mapping of the CLL tumor suppressor is described in the accompanying review paper. A significant part of Dr. Baranova's efforts is dedicated to in silico analysis of the publicly available genomics and proteomics database. Dr. Baranova sees these databases as treasure troves full of diamonds waiting to be unearthed and cut. While pursuing this line of research, Dr. Baranova and her Team has developed a novel method that allows high-throughput prediction of novel tumor markers by sorting publicly available EST sequences according to their tissue origin. Dr. Baranova's article published in FEBS Letters in 2001 received more than 40 citations. Since then, a number of the tumor marker sequences predicted by Dr. Baranova have been experimentally validated. Based on a computational prediction made by Dr. Panchin (Institute of Problems of Information Transmission, Russian Academy of Science), Dr. Baranova discovered and studied pannexins, a novel class of gap junction proteins present in both chordate and invertebrate genomes. As PANX2 expression levels can predict post-diagnosis survival for patients with glial tumors, pannexins may also be involved in the process of tumorigenesis. Dr. Baranova's experience in the development of methods facilitating discovery of tumor markers is equally applicable to other human chronic diseases. The past few years have added a novel focus to Dr. Baranova's research as she has gotten involved in collaboration with the Center for Liver Diseases at Inova Fairfax Hospital, Northern Virginia. In this collaboration, Dr. Baranova has published a number of papers uncovering molecular pathways altered in the pathogenesis of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis in morbidly obese patients and developed an ELISA-based diagnostic approach for the non-invasive detection of these diseases. Dr. Baranova, in her current role as a principle investigator at the Molecular and Microbiology Department at GMU directs a team of graduate researchers from various backgrounds including molecular and cell biology, statistics, and bioinformatics and employs a multidisciplinary approach in order to broaden research perspectives. She also teaches a number of graduate courses at MMB, including Biotechnology, Human Genetics and Cancer Biology, and Honor Seminar for undergraduates majoring in Biology. Dr. Baranova has published about 40 peer-reviewed scientific papers in international journals including Genomics, Hepatology, Clinical Cancer Research, FEBS Letter, Bioinformatics, Expert Reviews in Molecular Diagnostics, Leukemia and Lymphoma, Oncogene, and others. She is an active member of the Human Genome Organization, the American Society of Human Genetics (ASHG), and the Federation of European Biochemical Societies (FEBS). In 2007, Dr. Baranova received the Memorial A.V. Itkes Young Oncologist Award (2007) for a series of studies on B-cell chronic lymphocytic leukemia. She is also actively engaged in the process of science education for the general public and participates in ASHG's Geneticist-Educator Network of Alliances (GENA) Project as a Geneticist Partner. In 1999 she received an Award of the Russian Fund for Basic Research for the best article explaining scientific concepts to general public.


Gastrointestinal Stromal Tumors: Review Article

Fahad AL-Enezi, Khaled AL-Khaledy, Mahmood Labeeb, Amanguno Henny

  1. Fahad AL-Enezi
    Hussain Makki AL-Juma Center for Specialized Surgery
  2. Khaled AL-Khaledy
  3. Mahmood Labeeb
  4. Amanguno Henny

Gastrointestinal stromal tumors GISTs, precursors of interstitial cells of cajal, are rare mesenchymal tumors of the gastrointestinal tract that are highly resistant to chemotherapy and radiotherapy. The incidence of this rare disease is approximately 1.5 per 100,000 persons.1 The recent advances in immunohistochistry and molecular aspects increased the rate of accurate diagnosis. Imatinib is the standard first line systemic therapy for metastatic cases. Neoadjuvant treatment has been used for locally advanced tumors. Surgical resection is the primary modality for early, localized cases. Post-operatively, those who have high risk profiling will be candidates for adjuvant Imatinib. Resistance or intolerance will eventually develop in a significant proportion of patients while on Imatinib treatment. Many alternative therapies have been introduced. Suinitinb is approved as a second line of systemic treatment while many others are still investigational. This review will present the latest advances in the diagnostic and therapeutic aspects of GIST. The mechanism of action, side effects, of Imatinib as well as the patterns of resistance to this therapy will be presented. The radiological features of the primary disease and metastatic will be discussed. This review will address the role imaging modalities in evaluating the response to therapy. Molecular studies to confirm GIST as well as their potential role in predicting response to therapy are included in this review.

'The Medicine is to Get Me Better': Findings on Pediatric Cancer Patients' Responses to Play with Medical Equipment

Dr Pam McGrath, Nicole Rawson-Huff

  1. Dr Pam McGrath
  2. Nicole Rawson-Huff

Children coping with a haematological malignancy have to deal with an extensive number of stressors including frequent hospitalization, repeated intrusive procedures, and the stress of treatment and side-effects from prolonged chemotherapy. This article presents findings from recent qualitative research that documents through an unstructured play-based interview, which incorporated the opportunity to play with medical equipment, the insights and understanding of pediatric haematology patients about their disease and its treatment. This information is compared to baseline information on similar play-based interviews with a control group of healthy pre-schoolers. Although limitations to the comparison are noted, the significantly different results highlights the important of play as a medium for providing insights as to the knowledge, and meaning both healthy and seriously ill children bring to their understanding of leukaemia and related disorders. In summary, the healthy cohort of children displayed very short-lived, naive, uninformed, joyous encounters in playing with medical equipment, whilst the children with haematological malignancies demonstrated either intense and extended play or complete avoidance (aversion) accompanied by a detailed and quite sophisticated knowledge base and understanding of both the disease and its treatment.

Nucleolar Organizer Regions in Squamous Cell Carcinomas of the Uterine Cervix Treated with Chemoradiotherapy

Dr Takashi Nakano, Lin Kurnia, Yoshiyuki Suzuki, Budiningsih Siregar, Andri Andrijono, Irwan Ramli, Cholid Badri, Yukari Yoshida

  1. Dr Takashi Nakano
    Department of Radiation Oncology, Gunma University Graduate School of Medicine
  2. Lin Kurnia
  3. Yoshiyuki Suzuki
  4. Budiningsih Siregar
  5. Andri Andrijono
  6. Irwan Ramli
  7. Cholid Badri
  8. Yukari Yoshida

Background: Nucleolar organizer regions (NORs) are chromosomal loops of DNA involved in ribosomal synthesis. Their size and number in a nucleus has been reported to reflect the proliferative activities of various cells. The purpose of this study was to assess the meaning of the number of NORs in tumor-cell nucleoli compared with other proliferative markers before and after 10 Gy irradiation. Materials and Methods: Forty-six biopsy specimens from twenty three patients with cervical squamous cell carcinoma treated with chemo-radiotherapy at Cipto Mangun Kusumo Hospital (Indonesia) taken before radiotherapy and after exposure to 10 Gy were analyzed. The number of NORs was measured using a silver staining method. MIB-1 and p53 labeling indexes (LI) were measured using an immunohistochemical method. Histological radiation response and mitotic index (MI) were investigated with hematoxylin and eosin staining. Result: After 10 Gy irradiation, the number of NORs per nucleolus (AgNOR score) decreased from 4.9 to 3.4 (p<0.001). MIB-1-LI and MI increased from 26 to 39 (p<0.01) and from 0.006 to 0.012 (p<0.001), respectively. Before radiation therapy, a positive correlation was found between AgNOR score and MIB-1-LI (p=0.001) and between AgNOR score and MI (p=0.01). At 10 Gy, there was no significant correlation among number of NORs, MIB-1-LI, MI, or p53-LI. Histological radiation response had no correlation with AgNOR, MIB-1-LI, MI, or p53-LI. Conclusion: The number of NORs can be used as proliferative marker for assessing tumor cell proliferative activity before chemo-radiotherapy but not after 10 Gy irradiation.

Immunohistochemical Expression of CCND1 and p16 Genes in Tissue Micro-array

Sima Ataollahi Eshkoor, Patimah Ismail, Sabariah Abdul Rahman, Mirsaed Mirinargesi, Soraya Ataollahi Oshkour

  1. Sima Ataollahi Eshkoor
  2. Patimah Ismail
  3. Sabariah Abdul Rahman
  4. Mirsaed Mirinargesi
  5. Soraya Ataollahi Oshkour

Background and objectives: Immunohistochemistry using Tissue Micro-arrays (IHC-TMA) is a useful method to identify the alteration of CCND1 and p16 genes. This study determined the sensitivity of this analysis to find the protein over-expression of CCND1 and p16 in Basal Cell Carcinoma (BCC). Method: Twenty-five spot samples obtained from different patients who were diagnosed with BCC and four spot samples of normal skin tissue. The slides were assessed by IHC-TMA technique. Results: The study revealed this technique is a feasible and efficient method to diagnose the minute numbers of BCC cells in the skin tissue. It is a reliable method, which assesses a large number of samples in a research setting. This study illustrated a significant protein expression of CCND1 and p16 genes in TMA samples of 25 patients of BCC compared to normal skin tissue (p<0.05). The findings of this study demonstrated the over-expression of CCND1 and p16 proteins in BCC tissue samples using IHC-TMA method as compared to normal human skin tissue. Interpretation and Conclusion: Alteration of both CCND1 and p16 genes could lead to the abnormal proliferation activity in the cells and resulting in BCC.

Prolonged Progression-Free Survival with Recurrent Cancer Colon Patient Receiving Bevacizumab (Avastin) Maintenance: A Case Report

E Abdou, J Nemec, M Dawood, N Saad, E Anwar

  1. E Abdou
  2. J Nemec
  3. M Dawood
  4. N Saad
  5. E Anwar

Bevacizumab (Avastin or rhuMab VEGF) is a humanized monoclonal antibody targeting VEGF. VEGF is a critical determinant of tumor angiogenesis, a process that is a necessary component of tumor invasion, growth, and metastasis. VEGF expression by invasive tumors has been shown to correlate with vascularity and cellular proliferation and is prognostic for several human cancers. In 2004, FDA approved it in first line metastatic colorectal cancer with chemotherapy.1-2 Reported side effects due to bevacizumab are hypertension and increased risk of bleeding. Bowel perforation has also been reported.3

A Search for a Tumor Suppressor Gene Responsible for B-Cell Chronic Lymphocytic Leukemia: Old Leads and New Hopes

Aybike Birerdinc, Elizabeth Nohelty, Andre Marakhonov, Eugene Nikitin, Mikhail Skoblov, Vikas Chandhoke, Ancha Baranova

  1. Aybike Birerdinc
  2. Elizabeth Nohelty
  3. Andre Marakhonov
  4. Eugene Nikitin
  5. Mikhail Skoblov
  6. Vikas Chandhoke
  7. Ancha Baranova

Region q14 of human chromosome 13 harbors a critical tumor suppressor gene (TSG) for chronic lymphocytic leukemia and some other malignancies. Here we review the history of positional cloning attempts to identify a TSG for B-cell chronic lymphocytic leukemia (B-CLL) and evaluating all candidates for CLL TSG. A lack of open reading frames and mutations in DNA of CLL cells prompted the removal of DLEU1 and DLEU2 genes from the list of candidates. Some studies suggest a role of the alteration of the normal expression suppressor function of miRNAs located within 13q14. Other researchers continue to work with protein encoding genes located within the minimally deleted area, namely RFP2 and KCNRG. A haploin sufficiency model of CLL tumorigenesis has been proposed recently, stating that the inactivation of one copy of the tumor suppressor gene is enough to provide selective advantage or prevent apoptosis in progenitor cells of CLL. The involvement of the haploin sufficient genes in the process of tumorigenesis cannot be proven by mutation screenings, but requires thorough functional studies. As rearrangements of 13q14.3 are frequently found in other human tumors, particularly in multiple myeloma and prostate cancer, the importance of the elusive TSG located in 13q14.3 may be not limited to CLL. Therefore, all CLL TSG candidates should be subject to both mutational screening and functional studies in the malignant cells of non-lymphatic origin.

The Taiep Rat: A Neurological Mutant as a Model to Understand the Role of Glial Cells in Synaptic Transmission

Christian Bonansco, Marco Fuenzalida, Eduardo Couve, Esteban Aliaga, Manuel Roncagliolo

  1. Christian Bonansco
  2. Marco Fuenzalida
  3. Eduardo Couve
  4. Esteban Aliaga
  5. Manuel Roncagliolo

The Taiep rat, initially described as a myelin mutant, is now recognized for its reactive astrogliosis and the severe alterations of glutamatergic synaptic transmission in CNS. The mutant expresses a complex set of progressive molecular, morphological and functional alterations affecting oligodendrocytes, astrocytes and neurons. Here, we provide evidence that astrogliosis occurs in conjunction with asynchronic synaptic transmission and mislocalization of mGluRs in Taiep's hippocampus. These findings suggest that the mutation interferes key cellular functions, such as protein trafficking, affecting the modulation of neurotransmitter release mediated by astrocytes. Knowledge of neuropathological mechanisms in Taiep also provides an opportunity to establish correlates with neurological diseases in human beings presenting similar Taiep symptoms.

Pharmacogenomics of Cancer Chemotherapy

Godefridus J Peters

  1. Godefridus J Peters

Pharmacogenomics is the study of the role of the body's genetic inheritance on the response of a drug. Application of pharmacogenomics holds a great promise for guidance in individualized cancer chemotherapy. Until recently most chemotherapy was given to patients based on the pathology of the tumor. It was not possible to select patients otherwise. Many retrospective studies have been performed which resulted in a much more detailed knowledge on the factors which determine the patient's response to a certain treatment. Especially for certain drugs which show some activity and from which the mechanism of action was known, it was possible to determine these factors. These include a number of drugs affecting folate metabolism, such as the inhibition of thymidylate synthase by 5-fluorouracil treatment, methylation of thiopurines by thiopurine methyltransferase, and more recently the role of mutations in the epidermal growth factor receptor (EGFR) in sensitivity to drugs targeted against EGFR. In this review these and other drugs are being described in relation to predictive parameters, and how they can be used to individualize treatment.

Multiple Squamous Cell Carcinoma of Face in a Child with Xeroderma Pigmentosa: A Case Report

Dr Manas Ranjan Baisakh, Janet Khalkho, Mobarak A. Khan

  1. Dr Manas Ranjan Baisakh
    Consultant Oncopathologist, Panda Curie Cancer Hospital
  2. Janet Khalkho
  3. Mobarak A. Khan

Xeroderma pigmentosa is a rare autosomal recessive disease that manifests a spectrum of symptom complex ascribed to defective DNA repair on exposure to sunlight. The incidence of basal cell carcinoma & squamous cell carcinoma in these patients is 4500 times higher than general population.1 A seven year old child presented with pigmentation, freckling & multiple ulcerated lesion over face. On biopsy, it was diagnosed as squamous cell carcinoma. The details of this case are presented.

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